Mbappe wraps up big France win as Ronaldo bags hat-trick for Portugal in Thursday's FIFA World Cup qualifiers.
Antoine Griezmann put the home side ahead inside 14 minutes at the Stade de France before Kevin Strootman's sending-off led to the Dutch being overwhelmed in the final half hour.
Thomas Lemar scored twice, the first from a stunning volley, and Mbappe capped an already memorable day on a personal level by netting his first international goal at the death.
A far superior French side are firmly back on track in their quest to make it to Russia next year after their shock 2-1 defeat in Sweden in June. This result, coupled with Sweden's 3-2 defeat in Bulgaria, leaves Les Bleus three points clear at the top of qualifying Group A.
"A complete performance," was how France coach Didier Deschamps summed it up to TF1.
"It was a very positive match and we have another coming in three days (against Luxembourg). And I am not going to say that Sweden losing is a bad thing."
Meanwhile, after failing to make it to the 24-team Euro on French soil last year, the Netherlands are in a battle even to finish second and grab a place in the two-legged play-offs in November.
Dick Advocaat's side are fourth, three points behind second-placed Sweden with three qualifiers remaining, including a meeting with the Swedes in Amsterdam in October.
France should top the section and Deschamps has enough quality at his disposal for his team to be genuine contenders to win the World Cup.
At a packed Stade de France he left Mbappe on the bench at the start as the 18-year-old's loan move from Monaco to Paris Saint-Germain was made official little over an hour prior to kick-off.
New Barcelona winger Ousmane Dembele had not even been named in the squad, while Bayern Munich's Kingsley Coman won his first cap since the Euro 2016 final loss to Portugal at the same ground.
France were outstanding, opening the scoring when Djibril Sidibe found Griezmann and the Atletico Madrid forward played a one-two with Olivier Giroud before running into the box and finishing through the legs of goalkeeper Jasper Cillessen.
The Dutch were already struggling to stay in the game even before Strootman was dismissed just after the hour mark after picking up a second yellow card in a little over five minutes.
Arjen Robben squandered their best chance to equalise before Monaco winger Lemar put France out of sight in the 72nd minute, sending a stunning left-foot volley into the top-right corner after the ball broke to him on the edge of the box.
That was his first international goal, and he was provided with his second on a plate by Griezmann two minutes before the end.
There was still time for substitute Mbappe to sweep in a fourth, and for Robben to hit the bar on a miserable night for the Netherlands.
Currently serving a five-match ban in Spain with Real Madrid, Ronaldo showed no signs of ring-rustiness as he opened the scoring in Portugal's 5-1 win over the Faroe Islands in Oporto with an acrobatic volley inside three minutes.
He scored a penalty and went on to complete his hat-trick to make it 14 goals in this qualifying campaign and 78 international goals in 144 appearances for his country.
The reigning European champions, for whom William Carvalho and Nelson Oliveira also scored, are still three points behind Group B leaders Switzerland, whose 3-0 defeat of Andorra maintained their perfect record.
In Group H, PSG's Thomas Meunier and Romelu Lukaku both scored hat-tricks in Belgium's 9-0 drubbing of minnows Gibraltar that leaves them six points clear of Greece, held 0-0 by Estonia.